210 F. L. HORSFALL, JR. 



6. Levo-y-(o-cJdorobenzyl)-S-oxo-y-phenyl Caproic Acid 



This compound, termed caprochlorone, inhibits the multiplication of 

 influenza A virus in the de-embryonated egg (Liu et al., 1957a). In single-cycle 

 multiplication experiments (Liu et al., 1957a), 2 mg. of the compound per egg 

 prolonged the latent period and delayed multiplication when the compound 

 was present from to 1 hour, 2 to 4 hours, or 4 to 6 hours. Addition of the 

 compound at a later time had relatively little inhibitory effect. The earlier 

 the compound was added, the more pronounced was the prolongation of the 

 latent period. As judged from the final yield of virus, the inhibition produced 

 by a 1- or 2-hour exposure of the infected tissue to the compound was 

 relatively slight. However, when the compound was added at 2 hours and 

 not removed, the yield of virus was reduced to less than 1 % of control values. 

 The inhibitory effect on the production of soluble complement-fixing antigen 

 was less marked than on reproduction of the virus. 



Caprochlorone does not inactivate the infectivity of the virus in vitro, does 

 not affect adsorption of the agent by host cells, and does not reduce oxygen 

 uptake of host tissue. The effect on infected tissue is not irreversible and, on 

 removal of the compound, recovery of full capacity to support virus multi- 

 plication returns in 12 to 18 hours (Liu et al., 1957a). 



In the lung of the intact mouse, caprochlorone, when given by gavage, 3 to 

 4 mg. per dose, 3 times daily for 9 days, diminished the extent of pulmonary 

 lesions, mortality, and amount of virus produced if the inoculum was small 

 (Liu et al., 1957b). The yield of virus was approximately 10 % of that in 

 controls. The claim that the compound exerts a therapeutic effect in vivo 

 (Liu et al., 1957b) is mitigated by the fact that it was given at the time of 

 inoculation and was effective only when about 10 MLD 50 of virus was given. 

 The compound is toxic; 6 mg. causes death of chick embryos within 24 hours 

 (Liu et al., 1957a). There is no indication as to the mechanism of action. 



7. 5, Q-Dichloro-l-cc-jy-arabinopyranosylbenzimidazole (DAB) 



This compound, designated DAB, was also synthesized during a systematic 

 investigation of the inhibitory activity of glycosides of benzimidazoles in 

 relation to their chemical structure (Tamm, 1956b). It inhibits the multi- 

 plication of poliovirus, type 2, in monkey kidney cells in vitro (Tamm and 

 Nemes, 1957). 



In single-cycle multiplication experiments (Nemes and Tamm, 1958) the 

 compound at 0.34 mg. per milliliter markedly inhibited reproduction through- 

 out the latent period. Its effect was more striking when DAB was added at 

 3 hours than at 5 hours but was still obvious beyond the end of the latent 

 period. Like DRB described in an earlier section, DAB has no effect on the 

 infectivity of poliovirus in vitro (Tamm and Nemes, 1957) and probably 

 does not interfere with attachment or penetration of the virus. 



